Membrane disruption mechanism of antimicrobial peptides.

It has long been suggested that pore formation is responsible for the increase in membrane permeability by antimicrobial peptides (AMPs). To better understand the mechanism of AMP activity, the disruption of model membrane by protegrin-1 (PG-1), a cationic antimicrobial peptide, was studied using atomic force microscopy. I present here the direct visualization of the full range of structural transformations in supported lipid bilayer patches induced by PG-1, and compared the effects of PG-1 on membranes with different lipid compositions. The rich structural changes observed suggest that pore formation constitutes only an intermediate state along the route of the membrane disruption process by PG-1. The formation of these structures can be understood using a mesophase framework of a binary mixture of lipids and peptides, where PG-1 acts as an 1d detergent that reduce line tensions in membranes. Understanding the effect of lipid compositions on the structural transformation of supported lipid bilayers can help elucidate the mechanism of selective disruption towards bacterial from mammalian membranes by PG-1 and the emerge of antimicrobial resistance.